A phase I-II trial of gefitinib in combination with vinorelbine and oxaliplatin as salvage therapy in women with advanced ovarian cancer (AOC)

5020 Background: To evaluate activity and tolerability of gefitinib (Iressa) in combination with vinorelbine and oxaliplatin as salvage therapy in women with AOC. Methods: Women with AOC recurrent or refractory after ≥ 1 previous line of platinum-containing chemotherapy who had measurable disease by RECIST criteria or assessable by Ca-125 received oral gefitinib 250 mg/day with vinorelbine 25 mg/m2 and oxaliplatin 50 mg/m2 on days 1 and 8 every 3 weeks without prophylactic growth factor support. Gefitinib was continued until disease progression. Results: So far 33 patients (pts) have been entered, (10 CDDP-sensitive; 23 CDDP-refractory disease). Among the first 10 pts, 4 DLTs were observed in the first cycle (2 febrile neutropenias, 1 grade 4 neutropenia lasting >5 days, 1 grade 3 diarrhea) resulting in dose reduction for vinorelbine (20 mg/m2) and oxaliplatin (40 mg/m2). In the next 10 pts only 2 DLTs (febrile neutropenia and grade 4 neutropenia lasting >5 days) were observed and the study is ongoing as phase II. All pts were evaluable for toxicity and 29 (19 CDDP-refractory; 10 CDDP-sensitive) for response (2 too early, 1 protocol violation, 1 lost to follow up). Three complete (CR) and 2 partial responses (PR) were seen in the CDDP-refractory group (ORR 23.8%; 95%CI: 5.6–42.0%) and 4 CR with 5 PR in the CDDP-sensitive group (ORR 90%; 95%CI: 71.4–100%). Median duration of response was 5.2 months (range 1–6) for CDDP-refractory and 6.6 (range 1–10) for CDDP-sensitive; median time to progression was 4.1 months (range 1–14) and 8.6 (range 1–12), respectively. So far 8 pts have died (7 disease progression; 1 pulmonary embolism), 14 had disease progression, and 11 continue treatment. 134 cycles have been administered: median 3 (range 1–9) cycles per pt. Τoxicity included grade 3/4 neutropenia each in 8 (24%) pts, febrile neutropenia 4 (12%), grade 3 anemia 1 (3%), grade 3 diarrhea 3 (9%), neurotoxicity 1 (3%), rash 1 (3%) and transaminase elevation 1 (3%). Conclusions: The concurrent administration of gefitinib with vinorelbine and oxaliplatin is feasible and shows promising activity in pretreated pts with AOC. No significant financial relationships to disclose.